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MAD2 expression and its significance in mitotic checkpoint control in testicular germ cell tumour.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2007 Jun; Vol. 1773 (6), pp. 821-32. Date of Electronic Publication: 2007 Mar 28. - Publication Year :
- 2007
-
Abstract
- Chromosomal instability (CIN) is a common characteristic in testicular germ cell tumour (TGCT). A functional mitotic checkpoint control is important for accurate chromosome segregation during mitosis. Mitotic arrest deficient 2 (MAD2) is a key component of this checkpoint and inactivation of MAD2 is correlated with checkpoint impairment. The aim of this study was to investigate the function of mitotic checkpoint control in TGCT cells and to study its association with MAD2 expression using 8 TGCT cell lines as well as 23 TGCT tissue samples. We found that in response to microtubule disruption, 6 of 8 TGCT cell lines (75%) failed to arrest in mitosis demonstrated by the decreased mitotic index and aberrant expression of mitosis regulators, indicating that mitotic checkpoint defect is a common event in TGCT cells. This loss of mitotic checkpoint control was correlated with reduced MAD2 protein expression in TGCT cell lines implicating that downregulation of MAD2 may play a critical role in an impaired mitotic checkpoint control in these cells. In addition, immunohistochemistry studies on 23 seminomas and 12 normal testis tissues demonstrated that nuclear expression of MAD2 was much lower in seminomas (p<0.0001) but cytoplasmic MAD2 expression was higher in seminomas (p=0.06) than normal samples. Our results suggest that aberrant MAD2 expression may play an essential role in a defective mitotic checkpoint in TGCT cells, which may contribute to CIN commonly observed in TGCT tumours.
- Subjects :
- Adult
Aged
Aged, 80 and over
Cell Line, Tumor
Chromosome Segregation
Humans
Mad2 Proteins
Male
Middle Aged
Seminoma pathology
Testicular Neoplasms pathology
Testis metabolism
Testis pathology
Calcium-Binding Proteins biosynthesis
Cell Cycle Proteins biosynthesis
Chromosomal Instability
Down-Regulation
Gene Expression Regulation, Neoplastic
Mitosis
Nerve Tissue Proteins biosynthesis
Repressor Proteins biosynthesis
Seminoma metabolism
Testicular Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1773
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 17467818
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2007.03.014